Table Of ContentYichen Lu · Lixia Wang
Hongjin Duanmu · Chris Chanyasulkit Editors
Amie J. Strong · Hui Zhang Managing Editors
Handbook of Global
Tuberculosis Control
Practices and Challenges
Handbook of Global Tuberculosis Control
Yichen Lu • Lixia Wang
Hongjin Duanmu • Chris Chanyasulkit
Editors
Amie J. Strong • Hui Zhang
Managing Editors
Handbook of Global
Tuberculosis Control
Practices and Challenges
Editors Lixia Wang
Yichen Lu Chinese Nat’l Ctr Disease Control
Haikou VTI Biological Institute and Prevention
Boston, Massachusetts, USA Nat’l Center for TB Control & Prevention
Chinese Nat’l Ctr Disease Control
Hongjin Duanmu and Prevention
National Center for Tuberculosis Control Beijing, China
and Prevention
Chinese Center for Disease Control and Chris Chanyasulkit
Prevention Brookline, Massachusetts, USA
Beijing, China
Beijing Tuberculosis and Thoracic Tumor
Research Institute
Beijing Chest Hospital
Beijing, China
Managing Editors
Amie J. Strong
Vaccine Technologies, Inc.
Wellesley, MA
Hui Zhang
National Center for Tuberculosis Control
and Prevention
Chinese Center for Disease Control and
Prevention
Beijing, China
ISBN 978-1-4939-6665-3 ISBN 978-1-4939-6667-7 (eBook)
DOI 10.1007/978-1-4939-6667-7
Library of Congress Control Number: 2017933976
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Foreword
Tuberculosis (TB) is by most historical, forensic, and molecular analyses an ancient
disease that dates back to the dawn of human evolution and perhaps even earlier in
other animal species. Skeletal evidence of its existence has been observed in Greek
mummies and its symptoms were well described in the writings of Hippocrates
nearly 2500 years ago. It is not too surprising that a pathogen–host association that
is measured in millennia might provide unique and unprecedented challenges for
control by even the tools of modern medicine.
Over two billion people are thought to be infected by the causative organism of
TB, Mycobacterium tuberculosis, but remarkably most of these infections are
asymptomatic. Nonetheless, in the decade beginning in 2010, it has been estimated
that there are 10–20 million cases of active TB in the world and that these take a toll
of nearly 2 million lives a year with the developing world bearing most of this bur-
den. While the largest number of TB cases is tallied in some of the most populous
countries of the world (i.e., India, China, Indonesia, and Pakistan), many regions of
the world suffer higher rates of disease due to numerous factors including feeble
access to health care, poor nutrition, overcrowding, smoking, alcohol abuse, and the
high co-occurrence of multiple immunosuppressive conditions.
Despite the enormous advances in our understanding of the pathogenesis of TB as
an infectious disease, decades of various control measures, and new insights into fac-
tors that lead to outbreaks, we still find ourselves facing what amounts to only mar-
ginal improvements in the control of TB from a public health perspective. For
example, the implementation of a TB vaccine that is now nearly a century old (BCG)
has had very little measurable impact on disease incidence relative to other areas of
the world that don’t deploy this intervention. Antibiotic cocktails and treatment regi-
mens that include both old and new drug combinations can work with careful compli-
ance to suppress the disease and its transmission but are of limited use when faced
with resistant variants. Together vaccines and drug therapy have only modestly
slowed the evolutionary advance of M. tuberculosis as a formidable human pathogen.
Over the last few decades, the “perfect storm” presented by the global spread of the
immunosuppressive disease AIDS coupled with the emergence of multidrug resistant
variants of M. tuberculosis has provided a new selective milieu changing the fitness
v
vi Foreword
landscape of this pathogen. Although we now know the detailed genetic blueprint of
multiple isolates of this bacterial organism, this knowledge has, so far, not dramati-
cally accelerated the pace of genome-based discoveries such as the development of
new TB drugs or vaccine antigens. As a scientist, I find it both alarming and humbling
that the control of TB remains one of the most pressing challenges in global health
despite decades of effort to identify scientific solutions to this continuing problem.
It seems the timing is right to share our collective (indeed global) experiences in
areas that are important to TB control including (1) the role of vaccination, (2) strat-
egies for early detection and diagnosis, (3) effective drug therapy and suppression
of resistance, (4) transmission and outbreak control, and (5) the social and eco-
nomic factors that provide a framework for success or a pathway toward failure.
Thus, I read Handbook of Global Tuberculosis Control: Practices and Challenges
with great interest and applaud the effort of the superb editorial team (Yichen Lu,
Hongjin Duanmu, Lixia Wang, and Chris Chanyasulkit) and authoritative contribut-
ing authors in their assemble of this scholarly contribution. This discussion is timely
and critical to our understanding of the threat that TB represents and the tools we
have and need to develop to control its onslaught.
The book is organized in part through effective snapshots of individual countries
that are facing the challenge of TB. This provides the reader with a myriad of differ-
ent perspectives on the problem of TB control but through strategies that are shaped
by cultural and historical contexts, economic constraints, and human resources.
Some chapters provide customized blueprints for approaches to early detection, dis-
ease control, and prevention through the deployment of state-of-the-art technologi-
cal tools. Other chapters take on the challenge of providing updates on progress
toward improving public health countermeasures in the area of TB control such as
new developments in TB vaccine development efforts, diagnosis in the face of vac-
cination with cross-reactive immunogens such as BCG, and new treatment strate-
gies that suppress the development of resistance.
I believe Handbook of Global Tuberculosis Control: Practices and Challenges will
be of high interest to leadership and staff of organizations that focus on public health,
including governmental and nongovernmental agencies, academic institutions,
research centers, hospitals, and even businesses (particularly those engaged in various
aspects of addressing the TB problem). The content of the book may very likely influ-
ence the policies of such organizations, particularly those that are located within the
same geographical/political spheres that represent the book’s contributors.
TB is clearly an enormous problem in the developing world so understanding its
epidemiology, promising new tools in its control, and all practical experiences by
those facing this threat in the field are highly worthwhile aspirations for anybody
interested in international development. This is important knowledge for public health
practitioners, funding agencies, and all those interested in this enormous infectious
disease challenge—one that has the potential to continue to undermine efforts to
improve health and economic conditions for much of the world’s population. I highly
recommend this book to those engaged in all aspects of this critical global battle.
John J. Mekalanos
Department of Microbiology and Immunobiology
Harvard Medical School, Boston, MA, USA
Preface
This book is designed to provide a comprehensive overview of the global TB con-
trols for public health workers, infectious disease clinicians, researchers, and policy
makers worldwide. How to treat and prevent TB has challenged many generations
of public health workers before us, and it will continue to challenge future genera-
tions. It is important for the current generation to see where we are today in the
historical battle against this dreadful disease, how we got here, and where we are
going. Unlike smallpox, which had been eradicated a few decades ago, and polio,
which will be eradicated in the foreseeable future, tuberculosis infection in humans
is likely to remain and spread for a long time to come. We hope this book not only
helps many in the field of global TB control but also motivates more people to join
in this worthy cause.
Tuberculosis is considered a controllable human infectious disease. The current
TB vaccine, Bacille Calmette-Guérin (BCG), was invented more than a century ago
and has been used to vaccinate millions of people every year since the 1950s, mostly
in developing countries. The advent of antibiotics in the early part of the last century
has converted this oldest and deadliest human infectious disease into a curable
chronic disease. In fact, worldwide applications of directly observed treatment,
short-course (DOTS) strategy since the 1990s have achieved unprecedented success
in public health history. In many developing countries, especially in China, India,
Pakistan, and Indonesia, where more than half of the global population resides,
much of the modern public health infrastructure was built on the framework of gov-
ernment efforts to control TB.
By understanding how TB control works in these countries, readers of this book
can understand their public health systems, including the organizational frame-
works, disease information collection and management, and the ways in which pre-
ventive vaccines and disease treatment measures can reach cities, towns, and
villages. Such a basic understanding has become increasingly important ever since
the SARS epidemic in the beginning of this century, followed by the global panic
caused by the spread of H1N1 Flu and the most recent Ebola crisis. The threat of a
disastrous infectious disease pandemic has become so eminent that no public health
worker or even world leaders can ignore it. Many believe that the current global TB
vii
viii Preface
control infrastructure and experience will play critically important roles beyond TB
control. Several chapters in this book describe the history of current TB control
infrastructures and how they work at the national, provincial, county, and village
levels. Many of these authors come from some unusual places—high up in public
health, down “in the trenches”—and some of their knowledge has not been as acces-
sible to the western world until now. It is our hope that this book can give our read-
ers a better understanding of how public health systems function in the developing
world. Different countries like China, Japan, Pakistan, and Indonesia are presented
either in a country snapshot or as a case study. While these national public health
systems are totally different from each other, these outstanding national public
health workers have nevertheless achieved similar goals.
This seemingly “controllable” infectious disease, however, is still killing on aver-
age 4000 people a day worldwide with emerging new problems. More and more
public health workers worldwide are worried about the increasing appearance of
multidrug resistant (MDR) TB strains, the spread of which may take us back to the
pre-antibiotics era. Combined with the new global health crisis created by HIV/
AIDS in the past few decades, the unchecked spread of MDR-TB infection in
immune deficient human hosts may become the worst nightmare for public health
workers worldwide. Considering the more than 30 million people living with HIV/
AIDS worldwide and the more than 2 billion people living with latent TB infection
around the world, all public health workers and policy makers must be aware of the
imminent threat of MDR-TB to global public health. Several chapters in this book
specifically deal with MDR-TB with regard to various causes of treatment failures,
cost and efficacy of medications, identification and care of MDR patients, and much
more. The contributing authors of these chapters come from a wide range of exper-
tise from public health policy to hands-on medical treatment. Though chapters are
individually complete and the reader can select those of particular interest, taken
together, they offer a comprehensive look at the current field situation of the threat of
MDR-TB.
In addition to HIV/AIDS, there are other diseases that also significantly increase
TB rates in populations with high latent TB infections. A chapter in this book spe-
cifically describes these TB risk factors.
With years of working experience in TB clinics treating numerous patients with
suspected TB symptoms and thousands of confirmed TB patients with limited
medical means available, TB clinicians worldwide would benefit from exchanging
their valuable experiences and practices. Some of these TB clinicians contributed
theirs in a series of chapters in this book, which can either directly help their fel-
low TB clinicians elsewhere in the world or provide a showcase of the routine
medical practices in TB clinics to inspire academic and medical researchers to
translate their laboratory research into new TB diagnosis tools, treatments, and
even new TB vaccines.
Indeed, readers of this book may find it surprising that the unprecedented
advancement of medical science and modern technologies in the past few decades
has not translated into significant improvement of the clinical tools such as new TB
diagnosis methods and TB vaccines. The century-old BCG vaccine is not used in the
Preface ix
United States and most of the developed world. It is still being used to vaccinate
every reachable new born baby in developing countries, despite the fact that hun-
dreds of millions of these vaccinated infants have grown into adults who still con-
tract latent TB infections that may one day become active. The world obviously
needs a new and more effective TB vaccine. Similarly, the century-old TB diagnosis
method, the PPD skin test, is still being used in the majority of TB clinics and hos-
pitals worldwide, despite the fact that almost all of the people who received the
BCG vaccine in their early childhood—the majority of living populations in coun-
tries like China and India—can react positively to such a test. This technical short-
coming has made it very difficult for TB surveillance work in these countries to
achieve the desired results. Through some chapters of this book that specifically
discuss these issues, we hope more academic researchers will be motivated to
develop advanced TB diagnosis methods, TB vaccines, and more effective treat-
ment regimens.
Given the absence of new TB vaccines and diagnostic tools, this book includes
chapters that describe how TB clinicians handle their routine challenges. For exam-
ple, when dealing with a TB outbreak in close communities such as in college dorms
and classrooms, local public health workers and TB clinicians have been trying to use
anti-TB drugs to protect close contacts. Some people living with HIV/AIDS can also
be given preventative treatment if they also have latent TB infections.
New public health workers and students often feel that securing global TB con-
trol in today’s world is analogous to completing a colossal three-dimensional jigsaw
puzzle: it involves multiple, complex different parts at multiple levels, and while it
seems to be an attainable goal in theory, it can be nevertheless elusive in practice.
From a global TB control point of view, a world map based on the reported TB cases
in each country indeed looks like a mosaic plate (www.who.int). Three countries in
Asia (Cambodia, North Korea, and Burma) have more than 300 cases per 100,000
people. Whereas India has the most TB cases reported in the world, the prevalence
rate in India is actually in the same category as most other Asian countries such as
Pakistan, Afghanistan, Nepal, Bangladesh, Thailand, Malaysia, and Indonesia.
Although the prevalence rate in China is lower than in most of the neighboring
countries mentioned above, China still has the second largest number of TB patients
in the world. The situation in Africa is somewhat different. Almost all of the sub-
Saharan countries have reported to have more than 300 cases per 100,000 people,
including two of the region’s high GDP countries (South Africa and Botswana);
Tanzania and Angola stand out as the only two countries in the region where the
reported cases rates were significantly lower. There is a country in each region—
Japan in Asia and Egypt in Africa—which ranks in the lowest reported TB rate, with
less than 24 cases per 100,000 people, thus representing hope for TB control in Asia
and Africa. Many of us may attribute such results to the differences in each coun-
try’s social and economic conditions, especially their public health and medical care
systems, which obviously cannot be standardized or managed at a comparable level.
But readers of this book can find a very similar mosaic picture for the TB cases
reported in China, where a national standard does exist and a national public health
system is functioning. There is, therefore, no “one size fits all” plan for success;
x Preface
effective TB prevention and treatment programs are tailored to fit each region’s
particular conditions, logistics, and culture.
This book is also designed to remind us that today’s global health situation is
really quite far away from the goals of “an AIDS-free world” or “ending TB.” It is
urgently important that all governments realize the need for more investments in
bilateral and multilateral programs to address TB, in particular as HIV/AIDS, TB,
and malaria have been shown to be “three of the world’s greatest causes of morbid-
ity and mortality. The health crisis faced by the developing world, created by the
unchecked spread of HIV/AIDS, TB, and malaria, threatens to dramatically reverse
the hard-won development gains of the last 50 years” (American Public Health
Association Policy no. 200322). The importance of dealing with TB as a global
health priority is perhaps greater now than it ever has been—especially for the over-
all health and well-being of the human race. With globalization, the debilitating
social and economic disadvantage associated with TB burdens on developing coun-
tries threatens our broader global society. With the prevalence of MDR-TB, the
threat toward global society and its security becomes even more heightened. Finally,
recognizing that we live in an increasingly interconnected and interdependent
world, ending TB is truly a matter of social justice.
We thank Dr. John Mekalanos for writing the foreword of this book. Dr. Mekalanos
is the Chair of the Harvard Medical School’s Microbiology and Immunobiology
Department, and his laboratory is engaged in the analysis of bacterial virulence and
functional genomics. We truly believe that collaborative effort between medical aca-
demic researchers like Dr. Mekalanos and public health workers and TB clinicians
like many of the contributors of this book can result in breakthroughs that are much
needed in the field of global TB control. In the words of Dr. Gilla Kaplan, Director
of the TB program at the Bill & Melinda Gates Foundation, “To accelerate progress
against TB, research must be prioritized and reinvigorated. The discovery and devel-
opment of new and more efficient tools and delivery strategies will be essential to
achieve immediate and lasting gains against the epidemic.” We present this book as
a resource in this work and to facilitate transfer of information amongst researchers
entrenched in this work.
Boston, Massachusetts, USA Yichen Lu
Beijing, China Lixia Wang
Beijing, China Hongjin Duanmu
Brookline, Massachusetts, USA Chris Chanyasulkit
